Nanoarchitectonic Engineering of Thermal-Responsive Magnetic Nanorobot Collectives for Intracranial Aneurysm Therapy.

Stent-assisted coiling is a main treatment modality for intracranial aneurysms (IAs) in clinics, but critical challenges remain to be overcome, such as exogenous implant-induced stenosis and reliance on antiplatelet agents. Herein, an endovascular approach is reported for IA therapy without stent grafting or microcatheter shaping, enabled by active delivery of thrombin (Th) to target aneurysms using innovative phase-change material (PCM)-coated magnetite-thrombin (Fe3O4-Th@PCM) FTP nanorobots. The nanorobots are controlled by an integrated actuation system of dynamic torque-force hybrid magnetic fields. With robust intravascular navigation guided by real-time ultrasound imaging, nanorobotic collectives can effectively accumulate and retain in model aneurysms constructed in vivo, followed by controlled release of the encapsulated Th for rapid occlusion of the aneurysm upon melting the protective PCM (thermally responsive in a tunable manner) through focused magnetic hyperthermia. Complete and stable aneurysm embolization is confirmed by postoperative examination and 2-week postembolization follow-up using digital subtraction angiography (DSA), contrast-enhanced ultrasound (CEUS), and histological analysis. The safety of the embolization therapy is assessed through biocompatibility evaluation and histopathology assays. This strategy, seamlessly integrating secure drug packaging, agile magnetic actuation, and clinical interventional imaging, avoids possible exogenous implant rejection, circumvents cumbersome microcatheter shaping, and offers a promising option for IA therapy.

Metainterface Heterostructure Enhances Sonodynamic Therapy for Disrupting Secondary Biofilms.

Implant-related secondary infections are a challenging clinical problem. Sonodynamic therapy (SDT) strategies are promising for secondary biofilm infections by nonsurgical therapy. However, the inefficiency of SDT in existing acoustic sensitization systems limits its application. Therefore, we take inspiration from popular metamaterials and propose the design idea of a metainterface heterostructure to improve SDT efficiency. The metainterfacial heterostructure is defined as a periodic arrangement of heterointerface monoclonal cells that amplify the intrinsic properties of the heterointerface. Herein, we develop a TiO2/Ti2O3/vertical graphene metainterface heterostructure film on titanium implants. This metainterface heterostructure exhibits extraordinary sonodynamic and acoustic-to-thermal conversion effects under low-intensity ultrasound. The modulation mechanisms of the metainterface for electron accumulation and separation are revealed. The synergistic sonodynamic/mild sonothermal therapy disrupts biofilm infections (antibacterial rates: 99.99% for Staphylococcus aureus, 99.54% for Escherichia coli), and the osseointegration ability of implants is significantly improved in in vivo tests. Such a metainterface heterostructure film lays the foundation for the metainterface of manipulating electron transport to enhance the catalytic performance and holding promise for addressing secondary biofilm infections.

Gut bacteria-driven homovanillic acid alleviates depression by modulating synaptic integrity.

The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B. longum, or R. intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.

Efficacy of Wearable low-intensity pulsed Ultrasound treatment in the Movement disorder in Parkinson's disease (the SWUMP trial): protocol for a single-site, double-blind, randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is a progressive, neurodegenerative illness marked by the loss of dopaminergic neurons, causing motor symptoms. Oral levodopa replacement therapy remains the gold standard in the treatment of PD. It is, nevertheless, a symptomatic treatment. There is currently no effective treatment for PD. Therefore, new therapies for PD are highly desirable. Low-intensity pulsed ultrasound (LIPUS) has been shown to improve behavioral functions in PD animal models. It is a new type of neuromodulation approach that combines noninvasiveness with high spatial precision. The purpose of this study is to establish a new clinical protocol for LIPUS in the treatment of movement disorders in patients with PD. METHODS: This protocol is a single-site, prospective, double-blind, randomized controlled trial (RCT). Forty-eight participants with clinically confirmed PD will be randomly allocated to one of two groups: LIPUS group or sham group. All of the participants continue to use pharmacological therapy as a fundamental treatment. The primary outcome is the difference between groups from baseline to 4 months in the change in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score (part III). The secondary outcomes include the rating scales such as the Mini-Mental State Examination (MMSE), and other three rating scales, and medical examinations including high-density electroencephalography (hdEEG) and functional magnetic resonance imaging (fMRI). The primary safety outcome will be assessed at 4 months, and adverse events will be recorded. DISCUSSION: This study represents the clinical investigation into the efficacy of therapeutic LIPUS in the treatment of PD for the first time. If LIPUS is determined to be effective, it could offer a practical and innovative means of expanding the accessibility of ultrasound therapy by using a wearable LIPUS device within a home setting. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100052093. Registered on 17 October 2021.

Self-supplying Cu2+ and H2O2 synergistically enhancing disulfiram-mediated melanoma chemotherapy.

Disulfiram (DSF) can target and kill cancer cells by disrupting cellular degradation of extruded proteins and has therefore received particular attention for its tumor chemotherapeutic potential. However, the uncontrollable Cu2+/DSF ratio reduces the efficacy of DSF-mediated chemotherapy. Herein, self-supplying Cu2+ and oxidative stress synergistically enhanced DSF-mediated chemotherapy is proposed for melanoma-based on PVP-coated CuO2 nanodots (CPNDs). Once ingested, DSF is broken down to diethyldithiocarbamate (DTC), which is delivered into a tumor via the circulation. Under the acidic tumor microenvironment, CPNDs produce sufficient Cu2+ and H2O2. DTC readily chelates Cu2+ ions to generate CuET, which shows antitumor efficacy. CuET-mediated chemotherapy can be enhanced by H2O2. Sufficient Cu2+ generation can guarantee the maximum efficacy of DSF-mediated chemotherapy. Furthermore, released Cu2+ can be reduced to Cu+ by glutathione (GSH) and O2- in tumor cells, and Cu+ can react with H2O2 to generate toxic hydroxyl radicals (·OH) via a Fenton-like reaction, promoting the efficacy of CuET. Therefore, this study hypothesizes that employing CPNDs instead of Cu2+ ions could enhance DSF-mediated melanoma chemotherapy, providing a simple but efficient strategy for achieving chemotherapeutic efficacy.

Adaptive Multi-dimensional Weighted Network with Category-aware Contrastive Learning for Fine-grained Hand Bone Segmentation.

Accurately delineating and categorizing individual hand bones in 3D ultrasound (US) is a promising technology for precise digital diagnostic analysis. However, this is a challenging task due to the inherent imaging limitations of the US and the insignificant feature differences among numerous bones. In this study, we have proposed a novel deep learning-based solution for pediatric hand bone segmentation in the US. Our method is unique in that it allows for effective detailed feature mining through an adaptive multi-dimensional weighting attention mechanism. It innovatively implements a category-aware contrastive learning method to highlight inter-class semantic feature differences, thereby enhancing the category discrimination performance of the model. Extensive experiments on the challenging pediatric clinical hand 3D US datasets show the outstanding performance of the proposed method in segmenting thirty-eight bone structures, with the average Dice coefficient of 90.0%. The results outperform other state-of-the-art methods, demonstrating its effectiveness in fine-grained hand bone segmentation. Our method will be globally released as a plugin in the 3D Slicer, providing an innovative and reliable tool for relevant clinical applications. The source codes are available at https://github.com/Bolun-Z/HandAISegmentation.

Lactic acid responsive sequential production of hydrogen peroxide and consumption of glutathione for enhanced ferroptosis tumor therapy.

Ferroptosis is characterized by the lethal accumulation of lipid reactive oxygen species (ROS), which has great potential for tumor therapy. However, developing new ferroptosis-inducing strategies by combining nanomaterials with small molecule inducers is important. In this study, an enzyme-gated biodegradable natural-product delivery system based on lactate oxidase (LOD)-gated biodegradable iridium (Ir)-doped hollow mesoporous organosilica nanoparticles (HMONs) loaded with honokiol (HNK) (HNK@Ir-HMONs-LOD, HIHL) is designed to enhance ferroptosis in colon tumor therapy. After reaching the tumor microenvironment, the outer LOD dissociates and releases the HNK to induce ferroptosis. Moreover, the released dopant Ir4+ and disulfide-bridged organosilica frameworks deplete intracellular glutathione (GSH), which is followed by GSH-mediated Ir(IV)/Ir(III) conversion. This leads to the repression of glutathione peroxidase 4 (GPX4) activity and decomposition of intratumoral hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) by Ir3+-mediated Fenton-like reactions. Moreover, LOD efficiently depletes lactic acid to facilitate the generation of H2O2 and boost the Fenton reaction, which in turn enhances ROS generation. With the synergistic effects of these cascade reactions and the release of HNK, notable ferroptosis efficacy was observed both in vitro and in vivo. This combination of natural product-induced and lactic acid-responsive sequential production of H2O2 as well as the consumption of glutathione may provide a new paradigm for achieving effective ferroptosis-based cancer therapy.

Super-resolution imaging of urethral vasculature in healthy pre- and post-menopausal females.

Previous studies have postulated that the urethral vasculature (UV) might play an important role in urinary continence for women. The goal of this research was to compare the UV in pre- and post-menopausal women using a super-resolution ultrasound imaging method called Super Ultrasound for Greater Accuracy and Resolution (SUGAR). We found that post-menopausal women exhibited decreased UV parameters such as fractal dimension, vessel proportion, and mean blood vessel diameter than pre-menopausal women. We also discriminated the vascular pattern in several layers of the urethra and its surrounding in vivo, including the urethral mucosa and submucosa, urethral muscle, and anterior vaginal wall. Besides, the statistical analysis of the vasculature pattern showed that most of the UV parameters peaked at mid-urethra. Ultimately, the UV parameters exhibited a tendency of first increasing, then reducing, and finally decreasing with age.

Promoting collateral formation in type 2 diabetes mellitus using ultra-small nanodots with autophagy activation and ROS scavenging.

BACKGROUND: Impaired collateral formation is a major factor contributing to poor prognosis in type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease. However, the current pharmacological treatments for improving collateral formation remain unsatisfactory. The induction of endothelial autophagy and the elimination of reactive oxygen species (ROS) represent potential therapeutic targets for enhancing endothelial angiogenesis and facilitating collateral formation. This study investigates the potential of molybdenum disulfide nanodots (MoS2 NDs) for enhancing collateral formation and improving prognosis. RESULTS: Our study shows that MoS2 NDs significantly enhance collateral formation in ischemic tissues of diabetic mice, improving effective blood resupply. Additionally, MoS2 NDs boost the proliferation, migration, and tube formation of endothelial cells under high glucose/hypoxia conditions in vitro. Mechanistically, the beneficial effects of MoS2 NDs on collateral formation not only depend on their known scavenging properties of ROS (H2O2, •O2-, and •OH) but also primarily involve a molecular pathway, cAMP/PKA-NR4A2, which promotes autophagy and contributes to mitigating damage in diabetic endothelial cells. CONCLUSIONS: Overall, this study investigated the specific mechanism by which MoS2 NDs mediated autophagy activation and highlighted the synergy between autophagy activation and antioxidation, thus suggesting that an economic and biocompatible nano-agent with dual therapeutic functions is highly preferable for promoting collateral formation in a diabetic context, thus, highlighting their therapeutic potential.

Platinum-Loaded Cerium Oxide Capable of Repairing Neuronal Homeostasis for Cerebral Ischemia-Reperfusion Injury Therapy.

Effective neuroprotective agents are required to prevent neurological damage caused by reactive oxygen species (ROS) generated by cerebral ischemia-reperfusion injury (CIRI) following an acute ischemic stroke. Herein, it is aimed to develop the neuroprotective agents of cerium oxide loaded with platinum clusters engineered modifications (Ptn-CeO2). The density functional theory calculations show that Ptn-CeO2 could effectively scavenge ROS, including hydroxyl radicals (·OH) and superoxide anions (·O2 -). In addition, Ptn-CeO2 exhibits the superoxide dismutase- and catalase-like enzyme activities, which is capable of scavenging hydrogen peroxide (H2O2). The in vitro studies show that Ptn-CeO2 could adjust the restoration of the mitochondrial metabolism to ROS homeostasis, rebalance cytokines, and feature high biocompatibility. The studies in mice CIRI demonstrate that Ptn-CeO2 could also restore cytokine levels, reduce cysteine aspartate-specific protease (cleaved Caspase 3) levels, and induce the polarization of microglia to M2-type macrophages, thus inhibiting the inflammatory responses. As a result, Ptn-CeO2 inhibits the reperfusion-induced neuronal apoptosis, relieves the infarct volume, reduces the neurological severity score, and improves cognitive function. Overall, these findings suggest that the prominent neuroprotective effect of the engineered Ptn-CeO2 has a significant neuroprotective effect and provides a potential therapeutic alternative for CIRI.

Bone age assessment based on three-dimensional ultrasound and artificial intelligence compared with paediatrician-read radiographic bone age: protocol for a prospective, diagnostic accuracy study.

INTRODUCTION: Radiographic bone age (BA) assessment is widely used to evaluate children's growth disorders and predict their future height. Moreover, children are more sensitive and vulnerable to X-ray radiation exposure than adults. The purpose of this study is to develop a new, safer, radiation-free BA assessment method for children by using three-dimensional ultrasound (3D-US) and artificial intelligence (AI), and to test the diagnostic accuracy and reliability of this method. METHODS AND ANALYSIS: This is a prospective, observational study. All participants will be recruited through Paediatric Growth and Development Clinic. All participants will receive left hand 3D-US and X-ray examination at the Shanghai Sixth People's Hospital on the same day, all images will be recorded. These image related data will be collected and randomly divided into training set (80% of all) and test set (20% of all). The training set will be used to establish a cascade network of 3D-US skeletal image segmentation and BA prediction model to achieve end-to-end prediction of image to BA. The test set will be used to evaluate the accuracy of AI BA model of 3D-US. We have developed a new ultrasonic scanning device, which can be proposed to automatic 3D-US scanning of hands. AI algorithms, such as convolutional neural network, will be used to identify and segment the skeletal structures in the hand 3D-US images. We will achieve automatic segmentation of hand skeletal 3D-US images, establish BA prediction model of 3D-US, and test the accuracy of the prediction model. ETHICS AND DISSEMINATION: The Ethics Committee of Shanghai Sixth People's Hospital approved this study. The approval number is 2022-019. A written informed consent will be obtained from their parent or guardian of each participant. Final results will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200057236.

A fNIRS investigation of menopausal-related symptoms and brain cortical activity in menopause.

BACKGROUND: This study aimed to delineate the association between menopausal-related symptoms and brain cortical hemodynamics in peri-postmenopause women. METHODS: Cross-sectional data from a total of 358 Han-Chinese women who visited the Menopause Clinic in the Shanghai Sixth People's Hospital from August 2019 to August 2022. Menopausal-related symptoms were analyzed through Kupperman index (KMI) scale and PSQI scale, while cerebral blood flow was measured using a functional near-infrared spectroscopy (fNIRS). Multiple linear regression model was used to assess the risk factors for subregions of brain hemodynamic response. RESULTS: After adjusting for confounding factors, we identified that menopausal symptom (B = -1.575, 95 % CI (-2.661, -0.488), p = 0.005) and duration of menopause (B = -14.583, 95 % CI (-26.753, -4.192), p = 0.007) were independently associated with the lower brain hemodynamic response in the prefrontal lobe, while in the temporal lobe, overweight (BMI ≥ 24 kg/m2) was negatively associated with the lower brain cortical activity (B = -36.882, 95 % CI (-72.708, -1.056), p = 0.044) after adjusting for other confounding variables. CONCLUSIONS: Our findings proposed that menopausal symptom and overweight should be attached great importance to the postmenopausal women, which provides clinical evidence for the feasible early detection and effective prevention such as menopausal hormone therapy (MHT) of brain health in postmenopausal women.

Dual-Functional Laser-Guided Magnetic Nanorobot Collectives against Gravity for On-Demand Thermo-Chemotherapy of Peritoneal Metastasis.

Combining hyperthermic intraperitoneal chemotherapy with cytoreductive surgery is the main treatment modality for peritoneal metastatic (PM) carcinoma despite the off-target effects of chemotherapy drugs and the ineluctable side effects of total abdominal heating. Herein, a laser-integrated magnetic actuation system that actively delivers doxorubicin (DOX)-grafted magnetic nanorobot collectives to the tumor site in model mice for local hyperthermia and chemotherapy is reported. With intraluminal movements controlled by a torque-force hybrid magnetic field, these magnetic nanorobots gather at a fixed point coinciding with the position of the localization laser, moving upward against gravity over a long distance and targeting tumor sites under ultrasound imaging guidance. Because aggregation enhances the photothermal effect, controlled local DOX release is achieved under near-infrared laser irradiation. The targeted on-demand photothermal therapy of multiple PM carcinomas while minimizing off-target tissue damage is demonstrated. Additionally, a localization/treatment dual-functional laser-integrated magnetic actuation system is developed and validated in vivo, offering a potentially clinically feasible drug delivery strategy for targeting PM and other intraluminal tumors.

Chinese Ultrasound Doctors Association Guideline on Operational Standards for 2-D Shear Wave Elastography Examination of Musculoskeletal Tissues.

The Ultrasound Physician Branch of the Chinese Medical Doctor Association sought to develop evidence-based recommendations on the operational standards for 2-D shear wave elastography examination of musculoskeletal tissues. A consensus panel of 22 Chinese musculoskeletal ultrasound experts reviewed current scientific evidence and proposed a set of 12 recommendations for 13 key issues, including instruments, operating methods, influencing factors and image interpretation. A final consensus was reached through discussion and voting. On the basis of research evidence and expert opinions, the strength of recommendation for each proposition was assessed using a visual analog scale, while further emphasizing the best available evidence during the question-and-answer session. These expert consensus guidelines encourage facilitation of the standardization of clinical practices for collecting and reporting shear wave elastography data.

Maximum intensity projection based on high frame rate contrast-enhanced ultrasound for the differentiation of breast tumors.

Objective: We explored the role of maximum intensity projection (MIP) based on high frame rate contrast-enhanced ultrasound (H-CEUS) for the differentiation of breast tumors. Methods: MIP imaging was performed in patients with breast tumors who underwent H-CEUS examinations. The microvasculature morphology of breast tumors was assessed. The receiver operating characteristic curve was plotted to evaluate the diagnostic performance of MIP. Results: Forty-three breast tumors were finally analyzed, consisting of 19 benign and 24 malignant tumors. For the ≤30-s and >30-s phases, dot-, line-, or branch-like patterns were significantly more common in benign tumors. A tree-like pattern was only present in the benign tumors. A crab claw-like pattern was significantly more common in the malignant tumors. Among the tumors with crab claw-like patterns, three cases of malignant tumors had multiple parallel small spiculated vessels. There were significant differences in the microvasculature morphology for the ≤30-s and >30-s phases between the benign and malignant tumors (all p < 0.001). The area under the curve, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the ≤30-s phase were all higher than those of the >30-s phase for the classification of breast tumors. Conclusion: MIP based on H-CEUS can be used for the differentiation of breast tumors, and the ≤30-s phase had a better diagnostic value. Multiple parallel small spiculated vessels were a new finding, which could provide new insight for the subsequent study of breast tumors.

Ultrasonic neural regulation over two-dimensional graphene analog biomaterials: Enhanced PC12 cell differentiation under diverse ultrasond excitation.

Two-dimensional (2D) biomaterials, with unique planar topology and quantum effect, have been widely recognized as a versatile nanoplatform for bioimaging, drug delivery and tissue engineering. However, during the complex application of nerve repair, in which inflammatory microenvironment control is imperative, the gentle manipulation and trigger of 2D biomaterials with inclusion and diversity is still challenging. Herein, inspired by the emerging clinical progress of ultrasound neuromodulation, we systematically studied ultrasound-excited 2D graphene analogues (graphene, graphene oxide, reduced graphene oxide (rGO) and carbon nitride) to explore their feasibility, accessibility, and adjustability for ultrasound-induced nerve repair in vitro. Quantitative observation of cell differentiation morphology demonstrates that PC12 cells added with rGO show the best compatibility and differentiation performance under the general ultrasound mode (0.5 w/cm2, 2 min/day) compared with graphene, graphene oxide and carbon nitride. Furthermore, the general condition can be improved by using a higher intensity of 0.7 w/cm2, but it cannot go up further. Later, ultrasonic frequency and duty cycle conditions were investigated to demonstrate the unique and remarkable inclusion and diversity of ultrasound over conventional electrical and surgical means. The pulse waveform with power of 1 MHz and duty cycle of 50 % may be even better, while the 3 MHz and 100 % duty cycle may not work. Overall, various graphene analog materials can be regarded as biosafe and accessible in both fundamental research and clinical ultrasound therapy, even for radiologists without material backgrounds. The enormous potential of diverse and personalized 2D biomaterials-based therapies can be expected to provide a new mode of ultrasound neuromodulation.

Efficacy of low-intensity pulsed ultrasound in the treatment of COVID-19 pneumonia.

PURPOSE: As a public health emergency of international concern, coronavirus disease 2019 (COVID-19) still lacks specific antiviral drugs, and symptomatic treatment is currently the mainstay. The overactivated inflammatory response in COVID-19 patients is associated with a high risk of critical illness or even death. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of LIPUS therapy for COVID-19 pneumonia. MATERIALS AND METHODS: 62 patients were randomly assigned to a treatment group (LIPUS treatment area - Group 1; self-control area - Group 2) and an external control group (Group 3). The primary outcomes were the volume absorption rate (VAR) and the area absorption rate (AAR) of lung inflammation in CT images. RESULTS: After an average duration of treatment 7.2 days, there were significant differences in AAR and VAR between Group 1 and Group 2 (AAR 0.25 vs 0.12, p=0.013; VAR 0.35 vs 0.11, p=0.005), and between Group 1 and Group 3 (AAR 0.25 vs 0.11, p=0.047; VAR 0.35 vs 0.19, p=0.042). Neither AAR nor VAR was statistically different between Group 2 and Group 3. After treatment, C-reactive protein, interleukin-6, leukocyte, and fingertip arterial oxygen saturation (SaO2) improved in Group 1, while in Group 3 only fingertip SaO2 increased. CONCLUSION: LIPUS therapy reduced lung inflammation and serum inflammatory factor levels in hospitalized COVID-19 patients, which might be a major advancement in COVID-19 pneumonia therapy.

Single Atom Iron-Doped Graphic-Phase C3 N4 Semiconductor Nanosheets for Augmented Sonodynamic Melanoma Therapy Synergy with Endowed Chemodynamic Effect.

Sonodynamic therapy (SDT) is a non-invasive therapeutic modality with high tissue-penetration depth to induce reactive oxygen species (ROS) generation for tumor treatment. However, the clinical translation of SDT is restricted seriously by the lack of high-performance sonosensitizers. Herein, the distinct single atom iron (Fe)-doped graphitic-phase carbon nitride (C3 N4 ) semiconductor nanosheets (Fe-C3 N4 NSs) are designed and engineered as chemoreactive sonosensitizers to effectively separate the electrons (e- ) and holes (h+ ) pairs, achieving high yields of ROS generation against melanoma upon ultrasound (US) activation. Especially, the single atom Fe doping not only substantially elevates the separation efficiency of the e- -h+ pairs involved in SDT, but also can serve as high-performance peroxidase mimetic enzyme to catalyze the Fenton reaction for generating abundant hydroxyl radicals, therefore synergistically augmenting the curative effect mediated by SDT. As verified by density functional theory simulation, the doping of Fe atom significantly promotes the charge redistribution in the C3 N4 -based NSs, which improves their synergistic SDT/chemodynamic activities. Both the in vitro and in vivo assays demonstrate that Fe-C3 N4 NSs feature an outstanding antitumor effect by aggrandizing the sono-chemodynamic effect. This work illustrates a unique single-atom doping strategy for ameliorating the sonosensitizers, and also effectively expands the innovative anticancer-therapeutic applications of semiconductor-based inorganic sonosensitizers.

Weakly supervised real-time instance segmentation for ultrasound images of median nerves.

Medical ultrasound technology has garnered significant attention in recent years, with Ultrasound-guided regional anesthesia (UGRA) and carpal tunnel diagnosis (CTS) being two notable examples. Instance segmentation, based on deep learning approaches, is a promising choice to support the analysis of ultrasound data. However, many instance segmentation models cannot achieve the requirement of ultrasound technology e.g. real-time. Moreover, fully supervised instance segmentation models require large numbers of images and corresponding mask annotations for training, which can be time-consuming and labor-intensive in the case of medical ultrasound data. This paper proposes a novel weakly supervised framework, CoarseInst, to achieve real-time instance segmentation of ultrasound images with only box annotations. CoarseInst not only improves the network structure, but also proposes a two-stage "coarse-to-fine" training strategy. Specifically, median nerves are used as the target application for UGRA and CTS. CoarseInst consists of two stages, with pseudo mask labels generated in the coarse mask generation stage for self-training. An object enhancement block is incorporated to mitigate the performance loss caused by parameter reduction in this stage. Additionally, we introduce a pair of loss functions, the amplification loss, and the deflation loss, that work together to generate the masks. A center area mask searching algorithm is also proposed to generate labels for the deflation loss. In the self-training stage, a novel self-feature similarity loss is designed to generate more precise masks. Experimental results on a practical ultrasound dataset demonstrate that CoarseInst could achieve better performance than some state-of-the-art fully supervised works.